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工程循环细菌素:α-螺旋交换和二硫化物引入循环A中的结构和功能影响

Fangfang Liu¹, Auke J van Heel^1,2, Oscar P Kuipers^1,2

¹Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, Netherlands.

Frontiers in microbiology

|March 4, 2024

概括

这项研究设计了循环蛋白A,一种循环抗微生物 (AMP),以创造新的治疗方法. 修改揭示了结构约束,但证实了圆形细菌素.

科学领域:

微生物学和分子生物学
体工程是什么? 体工程是什么?
抗菌剂抗菌剂抗菌剂

背景情况:

圆形细菌素是通过核糖体合成和翻译后修饰的 (RiPPs),具有独特的头到尾结构.
它们的核糖体起源允许遗传多样化,使得它们成为抗微生物 (AMP) 开发的有希望的支架.
来自*Clostridium beijerinckii*的A环状物作为探索工程策略的模型.

研究的目的:

调查循环蛋白A在开发新型抗菌剂方面的工程潜力.
评估α螺旋修改和二硫化键引入对循环蛋白A生物合成和生物活性的影响.
评估圆形细菌素作为质工程的多功能支架.

主要方法:

通过引入囊蛋白来形成潜在的二硫化物键来改造循环蛋白A.
取代了循环蛋白A的五个α螺旋,用来自素AS-48.8的相应螺旋取代了它们.
评估了这些修改对生物合成和抗菌活性的影响.

主要成果:

导入二硫化键显著减少了循环A生物合成和/或生物活性,突出了α螺旋弹性的重要性.
在一个实例中,减少潜在的二硫化物键增强了抗菌活性.
替换α螺旋在某些情况下产生了适度活跃的,在功能转移方面表现出有限的成功.

结论:

体工程是可行的引入特定的结构性质到循环蛋白A.
工程循环细菌菌的结构和功能限制存在.
圆形细菌素是开发具有定制性质的新型抗微生物的合适支架.

关键词:

细菌素的工程学生物活性生物活性生物合成生物合成圆形的细菌素是圆形的细菌素.在圆形中A在A中.双硫化物键是一种二硫化物键.酸脚手架酸脚手架 α-螺旋轮替换器

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